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Cell polarity; biochemistry; developmental biology; and cell signaling and gene regulation Cell polarity involves the unequal distribution of molecules and/or organelles to particular regions of a cell. Such subcellular organization contributes to important aspects of cell growth and function. For example, motile fibroblasts sort the molecular machinery required for actin synthesis to the leading edge of their plasma membrane. This facilitates membrane ruffling and cellular motility. Oocytes, on the other hand, sort important regulatory molecules to create the diversity in gene expression that leads to pattern formation in embryos. We are interested in the molecular mechanisms responsible for generating cell polarity in oocytes and possibly other cell types. More specifically, our goal is to elucidate the molecular mechanism responsible for localizing the Vg1 mRNA to the vegetal cortex of Xenopus oocytes. Vg1 mRNA encodes a TGF-beta growth factor that induces mesoderm during embryonic development. Localization of the Vg1 mRNA is controlled by a ~360 nucleotide region of the Vg1 3' UTR referred to as the Vg1 localization element or VgLE. Vg1 localization requires components of the cytoskeleton and an RNA-binding protein called Vera. Vera is highly conserved in vertebrates and interacts specifically with the VgLE. A hallmark of RNA localization is that localized RNAs are associated with large particles called "RNA granules" that are transported along the cytoskeleton. These RNA granules consist of hundreds of RNA molecules and their associated proteins. Identifying specific RNA-protein and protein-protein interactions involved in the formation of RNA granules is, therefore, crucial for understanding the RNA localization process. To gain insights into the molecular aspects of RNA granule formation, we are using molecular genetics, biochemistry and micro-injection assays to: 1) characterize the specific RNA-protein interactions involved in Vera binding to the VgLE, 2) search for proteins that interact with Vera protein, and 3) search for additional RNA-binding proteins that specifically interact with the VgLE. Heinrich, B. & Deshler, J. O. 2008. RNA Localization to the Balbiani Body in Xenopus Oocytes is Regulated by the Energy State of the Cell and Facilitated by Kinesin II. RNA (Accepted for Publication). Andken, B.B., Lim, I., Benson, G., Vincent, J.J., Ferenc, M.T., Heinrich, B., Jarzylo, L.A., Man, H., J.O. Deshler. 2007. 3'-UTR SIRF: A Database for Identifying Clusters of Short Interspersed Repeats in 3'-Untranslated Regions. BMC Bioinformatics 2007, 8:274 (30 July 2007). BMC Bioinformatics 2007, 8:274 (30 July 2007). Choo, S., Heinrich, B., Betley, J. N., Chen, Z. & Deshler, J. O. 2005.Evidence for Common Machinery Utilized by the Early and Late RNA Localization Pathways in Xenopus Oocytes. Dev Biol 278, 103-117. Click here for PDF file. Betley, J. N., Heinrich, B., Vernos, I., Sardet, C., Prodon, F., and Deshler, J. O. 2004. Kinesin II meditates Vg1 mRNA transport in Xenopus oocytes. Curr Biol 14, 219-24. Click here for PDF file. Betley, J.N., Frith, M.C. Graber, J.H. Choo, S. and J.O. Deshler. 2002. A ubiquitous and conserved signal for RNA localization in chordates. Current Biology 12:1756-1761. Click here for PDF file. Deshler, J. O., Highett, M. I., Abramson, A., and Schnapp, B. J. 1998. A highly conserved RNA-binding protein for cytoplasmic mRNA localization in vertebrates. Current Biology 8, 489-496. Deshler, J. O., Highett, M. I., and Schnapp, B. J. 1997. Localization of Xenopus Vg1 mRNA by Vera protein and the endoplasmic reticulum [see comments]. Science 276, 1128-31. Schnapp, B. J., Arn, E. A., Deshler, J. O., and Highett, M. I. 1997. RNA location in xenopus oocytes [Review]. Seminars In Cell & Developmental Biology 8, 529-540. |
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If you would like to find out more information regarding James Deshler's research you can write to him at: 5 Cummington Street, Boston, MA 02215; call (617) 358-0444; or e-mail him at jdeshler@bu.edu. Questions
and comments are always welcome.
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